The human GABA(B1b) and GABA(B2) heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen

Br J Pharmacol. 2000 Nov;131(6):1050-4. doi: 10.1038/sj.bjp.0703682.

Abstract

1. The aim of this study was to characterize the pharmacological profile of the GABA(B1)/GABA(B2) heterodimeric receptor expressed in Chinese hamster ovary (CHO) cells. We have compared receptor binding affinity and functional activity for a series of agonists and antagonists. 2. The chimeric G-protein, G(qi5), was used to couple receptor activation to increases in intracellular calcium for functional studies on the Fluorimetric Imaging Plate Reader (FLIPR), using a stable GABA(B1)/GABA(B2)/G(qi5) CHO cell line. [(3)H]-CGP-54626 was used in radioligand binding studies in membranes prepared from the same cell line. 3. The pharmacological profile of the recombinant GABA(B1/B2) receptor was consistent with that of native GABA(B) receptors in that it was activated by GABA and baclofen and inhibited by CGP-54626A and SCH 50911. 4. Unlike native receptors, the GABA(B1)/GABA(B2)/G(qi5) response was not inhibited by high microMolar concentration of phaclofen, saclofen or CGP 35348. 5. This raises the possibility that the GABA(B1)/GABA(B2)/G(qi5) recombinant receptor may represent the previously described GABA(B) receptor subtype which is relatively resistant to inhibition by phaclofen.

MeSH terms

  • Animals
  • Baclofen / analogs & derivatives*
  • Baclofen / metabolism
  • Baclofen / pharmacology
  • CHO Cells
  • Cricetinae
  • Dose-Response Relationship, Drug
  • GABA Agonists / metabolism*
  • GABA Antagonists / metabolism*
  • GABA Antagonists / pharmacology
  • Humans
  • Receptors, GABA / metabolism*
  • Receptors, GABA-B / metabolism*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • GABA Agonists
  • GABA Antagonists
  • GABBR2 protein, human
  • Receptors, GABA
  • Receptors, GABA-B
  • phaclofen
  • gamma-Aminobutyric Acid
  • Baclofen
  • saclofen